The purpose of this project is to define the humoral and cellular immune responses that relate to immunodiagnosis, immunopathology and protective immunity in patients with lymphatic filariasis, onchocerciasis, and loiasis. Serologic assays for filarial infection based on IgG4 antibody detection have greatly enhanced specificity because the IgG4 subclass is 'restricted' from recognizing epitopes such as phosphocholine that are common constituents of parasitic and other infectious organisms. Such IgG4 responses have been shown to take 6-9 months to develop despite strong immune stimulation. A diagnosistic test for new or pre-patent onchocerciasis infections has been developed using a purified recombinant 16 kD protein (OV-16). Histopathologic and serologic evidence implicates the eosinophil and its granule proteins as a primary determinant of the posttreatment reactions seen in onchocerciasis and lymphatic filariasis; IL-5 appears to be the primary determinant of eosinophil responses. Populations with bancroftian filariasis or onchocerciasis have been examined to define immunologic parameters that distinguish "naturally immune" from infected individuals. A 43kD protein from infective larvae that may be a protective immunogen has been cloned from a W. bancrofti expression library, and the gene is being sequenced. Similar studies in onchocerciasis have also identified differentially recognized molecules, that are being purified.